Trial Outcomes & Findings for Treatment and Prognosis of Neurogenic Orthostatic Hypotension : A Prospective Randomized Study (NCT NCT02308124)

NCT ID: NCT02308124

Last Updated: 2021-10-19

Results Overview

Change of orthostatic SBP and DBP drop after 3-month medical treatment compared to initial results.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

87 participants

Primary outcome timeframe

after 3-month medical treatment

Results posted on

2021-10-19

Participant Flow

Participant milestones

Participant milestones
Measure
Midodrine Only
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Overall Study
STARTED
29
29
29
Overall Study
COMPLETED
23
21
21
Overall Study
NOT COMPLETED
6
8
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Midodrine Only
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Overall Study
Lost to Follow-up
6
6
6
Overall Study
Adverse Event
0
2
2

Baseline Characteristics

Treatment and Prognosis of Neurogenic Orthostatic Hypotension : A Prospective Randomized Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Midodrine Only
n=29 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=29 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=29 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Total
n=87 Participants
Total of all reporting groups
Age, Continuous
59.2 years
STANDARD_DEVIATION 17.7 • n=5 Participants
59.7 years
STANDARD_DEVIATION 13.4 • n=7 Participants
52.7 years
STANDARD_DEVIATION 16.2 • n=5 Participants
57.2 years
STANDARD_DEVIATION 16.0 • n=4 Participants
Sex: Female, Male
Female
14 Participants
n=5 Participants
17 Participants
n=7 Participants
15 Participants
n=5 Participants
46 Participants
n=4 Participants
Sex: Female, Male
Male
15 Participants
n=5 Participants
12 Participants
n=7 Participants
14 Participants
n=5 Participants
41 Participants
n=4 Participants
Region of Enrollment
Korea, Republic of
29 participants
n=5 Participants
29 participants
n=7 Participants
29 participants
n=5 Participants
87 participants
n=4 Participants
Supine systolic blood pressure
137.3 mmHg
STANDARD_DEVIATION 20.9 • n=5 Participants
124.5 mmHg
STANDARD_DEVIATION 18.5 • n=7 Participants
122.0 mmHg
STANDARD_DEVIATION 15.6 • n=5 Participants
127.9 mmHg
STANDARD_DEVIATION 19.4 • n=4 Participants
Supine diastolic blood pressure
83.2 mmHg
STANDARD_DEVIATION 12.8 • n=5 Participants
76.5 mmHg
STANDARD_DEVIATION 9.8 • n=7 Participants
76.9 mmHg
STANDARD_DEVIATION 10.4 • n=5 Participants
78.9 mmHg
STANDARD_DEVIATION 11.4 • n=4 Participants
Supine heart rate
68.0 Beats per Minute
STANDARD_DEVIATION 11.3 • n=5 Participants
66.7 Beats per Minute
STANDARD_DEVIATION 13.5 • n=7 Participants
67.0 Beats per Minute
STANDARD_DEVIATION 10.7 • n=5 Participants
67.2 Beats per Minute
STANDARD_DEVIATION 11.8 • n=4 Participants
Orthostatic systolic blood pressure change
-24.7 mmHg
STANDARD_DEVIATION 9.9 • n=5 Participants
-23.3 mmHg
STANDARD_DEVIATION 12.5 • n=7 Participants
-22.5 mmHg
STANDARD_DEVIATION 10.1 • n=5 Participants
-23.5 mmHg
STANDARD_DEVIATION 10.8 • n=4 Participants
Orthostatic diastolic blood pressure change
-13.4 mmHg
STANDARD_DEVIATION 9.0 • n=5 Participants
-15.5 mmHg
STANDARD_DEVIATION 9.9 • n=7 Participants
-13.4 mmHg
STANDARD_DEVIATION 8.2 • n=5 Participants
-14.1 mmHg
STANDARD_DEVIATION 9.0 • n=4 Participants

PRIMARY outcome

Timeframe: after 3-month medical treatment

Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)

Change of orthostatic SBP and DBP drop after 3-month medical treatment compared to initial results.

Outcome measures

Outcome measures
Measure
Midodrine Only
n=23 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=21 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=21 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Change in Orthostatic BP Drop
Changes in DBP drop
7.5 mmHg
Standard Deviation 15.3
11.1 mmHg
Standard Deviation 17.7
7.4 mmHg
Standard Deviation 14.2
Change in Orthostatic BP Drop
Changes in SBP drop
11.1 mmHg
Standard Deviation 16.9
13.6 mmHg
Standard Deviation 20.1
8.9 mmHg
Standard Deviation 9.9

SECONDARY outcome

Timeframe: after 3-month medical treatment.

Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)

Change of the OH associated symptom survey result after 3-month medical treatment compared to initial results. OHQ questionnaire has two components: the OH daily activity scale (OHDAS), which contains 4 items measuring the impact of OH on daily activities, and the OH symptom assessment (OHSA), which contains 6 items measuring the symptoms of OH (dizziness/light headedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort).This questionnaire reflects the severity of OH-related symptoms on a 10-point scale, with 0 indicating the absence of a symptom and 10 indicating maximal severity. \*\* OHQ total score minimal 0 \~ maximal 100

Outcome measures

Outcome measures
Measure
Midodrine Only
n=23 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=21 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=21 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)).
-16.2 points
Standard Deviation 15.5
-17.2 points
Standard Deviation 20.3
-12.6 points
Standard Deviation 14.8

SECONDARY outcome

Timeframe: after 3-month medical treatment.

Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)

Change of the depression score after 3-month medical treatment compared to initial results. 21 multiple-choice questions, each of which can be scored from 0 to 3. Higher score represent higher degree of depression. Score Normal; 0-13, Mild depression; 14-19, Moderate depression; 20-28, Severe depression; 29-63

Outcome measures

Outcome measures
Measure
Midodrine Only
n=23 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=21 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=21 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Change of the Depression Score (Beck Depression Inventory-II )
-6.8 points
Standard Deviation 5.6
-7.8 points
Standard Deviation 6.5
-3.5 points
Standard Deviation 8.0

SECONDARY outcome

Timeframe: changes at 3 months after treatment

Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)

changes in Short Form (36) Health Survey version 2 (SF-36v2) physical component summary scale (PCS) compared to the baseline SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores.

Outcome measures

Outcome measures
Measure
Midodrine Only
n=23 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=21 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=21 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Short-form 36 Version 2
5.6 points
Standard Deviation 6.8
4.2 points
Standard Deviation 9.1
2.7 points
Standard Deviation 7.0

SECONDARY outcome

Timeframe: changes at 3 months after treatment

Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)

changes in Short Form (36) Health Survey version 2 (SF-36v2) mental component summary scale (MCS) SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores.

Outcome measures

Outcome measures
Measure
Midodrine Only
n=23 Participants
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=21 Participants
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=21 Participants
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Changes in Health-related Quality of Life
5.0 points
Standard Deviation 8.6
6.7 points
Standard Deviation 8.9
0.4 points
Standard Deviation 11.2

Adverse Events

Midodrine Only

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Pyridostigmine Only

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Midodrine + Pyridostigmine

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Midodrine Only
n=29 participants at risk
Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary.
Pyridostigmine Only
n=29 participants at risk
Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary.
Midodrine + Pyridostigmine
n=29 participants at risk
Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary.
Nervous system disorders
Headache
3.4%
1/29 • Number of events 1 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
6.9%
2/29 • Number of events 2 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
0.00%
0/29 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
Nervous system disorders
dizziness
3.4%
1/29 • Number of events 1 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
17.2%
5/29 • Number of events 5 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
3.4%
1/29 • Number of events 1 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
Gastrointestinal disorders
nausea
0.00%
0/29 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
6.9%
2/29 • Number of events 2 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
6.9%
2/29 • Number of events 2 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
Nervous system disorders
tremor
0.00%
0/29 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
3.4%
1/29 • Number of events 1 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.
0.00%
0/29 • Possible side effects were checked by direct questioning at each visit at 1 and 3 months after treatment. Expected adverse reactions were listed in the protocol.

Additional Information

Jung-Ick Byun

SNUH

Phone: +8224406254

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place